This invention relates to methods of treating, inhibiting or preventing vascular thrombosis and methods of treating, inhibiting or preventing arterial restenosis resulting from excessive intimal hyperplasia.
A thrombosis, i.e, the formation or presence of a blood clot within a blood vessel, may result from physical injury of an arterial wall by a vascular interventional procedure such as percutaneous transluminal coronary angioplasty ("PTCA"; a type of balloon angioplasty) or coronary bypass surgery. Thrombosis may also result from progression of a natural disease, such as atherosclerosis. Various agents, including aspirin, prostaglandin E.sub.1, selective thromboxane A.sub.2 inhibitors, selective thrombin inhibitors, platelet receptor GPIIb/IIIa blockers, tissue plasminogen activator, streptokinase, heparin and kistrin have been used as antithrombotics. See, e.g., Yasuda et al. (Circulation 83:1038 (1991)); and Gold et al., (Circulation (Supplement IV) 83:IV26 (1991)). Currently available antiplatelet agents include aspirin, ticlopidin, monoclonal antibodies, nitroglycerin and sodium nitroprusside.
Another unwanted result of arterial injury from vascular interventional procedures is arterial restenosis. For example, PTCA has been used extensively to open occluded arteries in both the coronary and peripheral vascular systems. Although initially successful in over 95 percent of cases, a gradual renarrowing or reocclusion process, known as restenosis, occurs within six months in 30 to 50 percent of the patients.
Vascular interventional procedures tend to damage the vascular wall. Such injury triggers the proliferation of vascular smooth muscle cells, resulting in intimal hyperplasia. This proliferation may be due in part to the effects of platelet-derived growth factors released by platelets which adhere to the site of arterial injury. Excessive intimal hyperplasia leads to restenosis, i.e., a re-narrowing of the arterial lumen. Thus, arterial restenosis can severely limit the long-term effectiveness of vascular interventional procedures.